It has been made clear in the past that the male hormone androgen plays an important role in prostate cancer, benign prostatic hypertrophy, male pattern baldness, sexual precociousness, common acne, seborrhea and hypertrichosis. For example, it is known that persons who have been castrated and persons suffering from sexual gland failure almost never develop prostate cancer or benign prostatic hypertrophy.
For example, cyproterone acetate, chlormadinone acetate, flutamide, bicalutamide and the like are used as anti-androgen agents, i.e., androgen receptor antagonists. These anti-androgen agents show an effect in many cases such as drug therapy in prostate cancer, and constitute important treatment drugs in this area. Furthermore, it is known that cyproterone acetate suppresses the occurrence of baldness and the progression of acne in teenagers. Furthermore, in females, cyproterone acetate is used in the treatment of androgenization and hair loss. Flutamide and bicalutamide are used as prostate cancer treatment agents.
However, as problems encountered in these anti-androgen agents, it is known that even if the anti-androgen agents are effective, the disorder recurs in almost all cases in two to five years, and in such cases, androgen resistance appears.
Furthermore, it has been reported that hydroxyflutamide, which is the active form of flutamide, causes an increase in androgen receptor transcription activity at a concentration of 10 μmol/L. Moreover, the hydroxyflutamide concentration in the blood in prostate cancer patients treated with flutamide is several μmol/L. However, it has been reported that this concentration reaches a concentration at which hydroxyflutamide shows an agonist effect (see Non-patent Document 1).
Furthermore, it has been reported that there is an increase in the weight of the prostate gland when cyproterone acetate and chlormadinone acetate are continuously administered to castrated rats for two weeks (see Non-patent Document 2). Moreover, in regard to flutamide and bicalutamide, there are also reports of side effects such as liver toxicity and the like. Accordingly, there is a demand for an anti-androgen agent which has a sufficient antagonistic effect, and in which these problems have been solved.
Meanwhile, the compounds represented by the following formula described in Japanese Patent Application No. 4-308579 A (Patent Document 1) and the corresponding European Patent Application No 494819 A (Patent Document 2) are known as phenylimidazolidines that show anti-androgen activity.

Furthermore, the compounds represented by the following formula described in Japanese Patent Application No. 10-510845 A (Patent Document 3) and the corresponding International Patent Publication WO 97/00071 (Patent Document 4) are known as substituted phenylimidazolidiens that show anti-androgen activity.

However, the compounds likewise do not constitute means for solving the problems of existing anti-androgen agents.    [Patent Document 1]
Japanese Patent Application No. 4-308579 A    [Patent Document 2]
European Patent Application No 494819 A    [Patent Document 3]
Japanese Patent Application No. 10-510845 A    [Patent Document 4]
International Patent Publication WO 97/00071    [Non-patent Document 1]
J. Biol. Chem., Vol. 270, pp. 19998-20003, 1995    [Non-patent Document 2]
Journal of the Endocrine Society of Japan, Vol. 66, pp. 597-606, 1990